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人类和小鼠肾单位发育的原理。

Principles of human and mouse nephron development.

机构信息

Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at University of Southern California, Los Angeles, CA, USA.

出版信息

Nat Rev Nephrol. 2022 Oct;18(10):628-642. doi: 10.1038/s41581-022-00598-5. Epub 2022 Jul 22.

Abstract

The mechanisms underlying kidney development in mice and humans is an area of intense study. Insights into kidney organogenesis have the potential to guide our understanding of the origin of congenital anomalies and enable the assembly of genetic diagnostic tools. A number of studies have delineated signalling nodes that regulate positional identities and cell fates of nephron progenitor and precursor cells, whereas cross-species comparisons have markedly enhanced our understanding of conserved and divergent features of mammalian kidney organogenesis. Greater insights into the complex cellular movements that occur as the proximal-distal axis is established have challenged our understanding of nephron patterning and provided important clues to the elaborate developmental context in which human kidney diseases can arise. Studies of kidney development in vivo have also facilitated efforts to recapitulate nephrogenesis in kidney organoids in vitro, by providing a detailed blueprint of signalling events, cell movements and patterning mechanisms that are required for the formation of correctly patterned nephrons and maturation of physiologically functional apparatus that are responsible for maintaining human health.

摘要

小鼠和人类肾脏发育的机制是一个研究热点。对肾脏发生的深入了解有可能指导我们理解先天性异常的起源,并使遗传诊断工具得以组装。许多研究已经描绘了调节肾祖细胞和前体细胞位置身份和细胞命运的信号节点,而跨物种比较极大地增强了我们对哺乳动物肾脏发生的保守和不同特征的理解。对近端-远端轴建立过程中发生的复杂细胞运动的更深入了解,挑战了我们对肾单位模式形成的理解,并为人类肾脏疾病发生的复杂发育背景提供了重要线索。体内肾脏发育研究还通过提供信号事件、细胞运动和模式形成机制的详细蓝图,促进了在体外肾类器官中肾发生的再现,这些信号事件、细胞运动和模式形成机制是形成正确模式化的肾单位和成熟具有生理功能的器官所必需的,这些器官负责维持人类健康。

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